[Influence of insulin-like growth factor 1 on PECAM-1 and ICAM-1 adhesion molecules expression in tumor necrosis factor alpha and hyperglycemia induced umbilical vein endothelial cells].
Activation, proliferation and regeneration of endothelium form developmental background of many pathological states. In those processes adhesion molecules and growth factors are crucial. Insulin-like growth factor 1 (IGF-1) is an important regulator of vascular function, capable of expressing pleiotropic actions. Interactions between endothelial cells and growth factors are complex and environment dependent. Cytokines, including tumor necrosis factor alpha (TNF-alpha) activate endothelium cells during inflammatory process. Endothelial dysfunction, with enhanced adhesion molecules expression, can be caused also by hyperglycemia. Aim of the study was to assess the influence of IGF-1 on platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) and intercellular adhesion molecule 1 (ICAM-1; CD54) expression on human umbilical vein endothelial cells (HUVECs) stimulated by hyperglycemia and TNF-alpha.


METHODS
Material for the study was obtained from fresh umbilical cord. Cell cultures were incubated with IGF-1 concentrations of 50 ng/ml and 200 ng/ml, glucose concentrations of 11.1 mmol/l and 22.2 mmol/l, TNF-alpha concentrations of 10 ng/ml and 20 ng/ml, as well as combinations of above. Ratio of PECAM-1 and ICAM-1 expression revealing cells was obtained using flow cytometry method. In statistic analysis ANOVA test and Duncan's new multiple range test were used.


RESULTS
It was demonstrated, that IGF-1 concentrations of 50 ng/ml, 200 ng/ml enhance PECAM-1 and ICAM-1 endothelial cells expression (respectively to 57.2 +/- 4.8%, 76.1 +/- 1.5% and 91.7 +/- 5.0%, 86.8 +/- 4.7%) compared to control group (respectively: 20.9 +/- 0.5% and 26.6 +/- 0.5%). Expression under influence of 10 ng/ml and 20 ng/ml TNF-alpha increases up to respectively: 78.4 +/- 0.9% and 86.5 +/- 0.7% for CD31 and respectively: 65.1 +/- 3.8% and 70.8 +/- 1.4% for CD54. Glucose concentration of 22.2 mmol/l increases CD31 expression to 44.6 +/- 5.2% and CD54 expression to 47.3 +/- 4.8%. Combination of influence of IGF-1 and hyperglycemia enhances CD31 expression from 82.2 +/- 0.6% up to 85.3 +/- 0.7%, whereas CD54 expression from 89.3 +/- 3.5% up to 94.4 +/- 0.5%, depending of concentrations. Combination of 20 ng/ml TNF-alpha with 50 ng/ml IGF-1 enhances expression of CD54 to 96.8 +/- 1.2%, with 200 ng/ml IGF-1 enhances CD31 and CD54 expression respectively to 90.5 +/- 2.3% and 96.6 +/- 0.6%.


CONCLUSIONS
1. It was concluded, that IGF-1, hyperglycemia and TNF-alpha enhance PECAM-1 and ICAM-1 adhesion molecules expression on HUVEC cells, activating the endothelium. 2. Combination of IGF-1, TNF-alpha and hyperglycemia influence synergistically enhances PECAM-1 and ICAM-1 expression on endothelial cells surface.
Wnuczko
Krzysztof
K
Kliniki Neonatologii i Intensywnej Terapii Noworodka Uniwersyteckiego Szpitala Klinicznego w Białymstoku. wnuczko@amb.edu.pl
Szczepański
Marek
M
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism* / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014471:Umbilical Veins
D018970:Insulin-Like Growth Factor Binding Protein 1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1